CN102600495A - Absorbable hemostatic composition and preparation method thereof - Google Patents
Absorbable hemostatic composition and preparation method thereof Download PDFInfo
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- CN102600495A CN102600495A CN2011100215156A CN201110021515A CN102600495A CN 102600495 A CN102600495 A CN 102600495A CN 2011100215156 A CN2011100215156 A CN 2011100215156A CN 201110021515 A CN201110021515 A CN 201110021515A CN 102600495 A CN102600495 A CN 102600495A
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Abstract
The invention relates to an absorbable hemostatic composition and a preparation method thereof. The absorbable hemostatic composition is prepared by mixing chitosan (or its derivatives), collagen and hyaluronic acid (or its salts and derivatives) as main hemostatic matrix. The main components of the absorbable hemostatic composition are hyaluronic acid and chitosan. The collagen is animal-derived collagen extracted from cattle, pig and fish, and/or recombinant human-derived collagen and/or collagen fragment. The absorbable hemostatic composition is obtained by combining hyaluronic acid and/or collagen with chitosan, and has rapid hemostatic effect on different wounds at different parts. The rapid hemostatic effect of the absorbable hemostatic composition is demonstrated by experiments.
Description
Technical field
The present invention relates to the good hemostatic composition of a kind of haemostatic effect.The invention belongs to novel hemostatic material technical field, it is simple especially to relate to a kind of preparation, good biocompatibility, and effect is remarkable, absorbable hemostatic material and preparation method thereof.
Background technology
At the emergency treatment of sudden accident, the wound hemostasis in the operation process, patient part quick-acting haemostatic powder effectively is extremely important.The hemostatic material of report mainly contains powdery type (zeolite, collagen powder and potato starch), mandruka (gelfoam, collagen sponge), oxidized regenerated cellulose and Fibrin Glue etc. at present; They each have certain weak point: gelatin and collagen organize adhesive force relatively poor; Both hemostatic functions all depend on the platelet and the thrombin of capacity, are restricted so use; Fibrin glue is derived from blood, may cause viral infection; Can emit a large amount of heat behind porous zeolite and the potato starch moisture in absorbing blood, cause the wound inflammation.
Along with the raising that China's medical circle requires the hemostatic material anthemorrhagic performance, it is imperative to develop the better material of haemostatic effect.At first, will possess good anthemorrhagic performance as the material of bleeding-stopping dressing or hemorrhage, good biocompatibility has no side effect, and nonirritant is easy to machine-shaping etc.Therefore, from existing condition, seeking the good biomaterial of occurring in nature and processing, improve just becomes a kind of ideal selection.Secondly, performance that can be different according to various hemostatic materials adopts the method for multiple hemostatic material coupling, makes material bring into play better anthemorrhagic performance.The associating of chitosan and collagen utilizes hydrogen bond action, electrostatic interaction between protein and saccharide exactly, adds being cross-linked with each other between groups such as amido, hydroxyl and improves mechanical strength, thereby more effectively reach the hemostatic purpose.
Summary of the invention
The object of the invention is intended to provide the novel absorbable hemostatic composition with excellent hemostatic function; Utilize chitosan to have characteristics such as nontoxic, no antigen, antibiotic property, excellent biological compatibility, degradable, promotion wound healing and antiinflammatory action; With the good automatically cross-linked hyaluronic acid of the miscible back of collagen and hemostatic function and biocompatibility for mixing, preparing can the absorbable novel hemostatic composition of quick-acting haemostatic powder.
The present invention adopts following technical scheme:
A kind of novel absorbable hemostatic composition comprises hyaluronic acid, collagen and chitosan, and hyaluronic acid, collagen and chitosan three weight ratio are 0.01～100:0.01～100:1.
More excellent scheme is: described hyaluronan molecule amount is 10,000-5,000,000; Described collagen is that the deacetylation of described chitosan is 40-95% from the humanized's of the animal derived collagen of cattle, pig, fish extraction and/or reorganization collagen and/or collagen fragment.
Another object of the present invention is to provide a kind of preparation technology of absorbable hemostatic composition.
For realizing above-mentioned purpose, the present invention adopts following technical scheme:
A kind of method for preparing of novel absorbable hemostatic composition comprises the steps:
1): with at least a being dissolved in the chitosan solution in hyaluronic acid or the collagen; If chitosan and collagen are placed hyaluronic acid solution; Chitosan and hyaluronic weight ratio are 0.01～100:0.01～100:1 in the solution, obtain mixed solution A behind the room temperature high-speed stirred 1-100min.
2): A is placed the hemostasis mould, form sthptic sponge B after the lyophilization.
3): B obtains finished product behind sterilization roentgenization 1-120min.
Alternative scheme is: in the step 1) with chitosan with or collagen be dissolved in the acid solutions such as acetum or formic acid solution of 0.1-30% (v/v), the acid solution that is dissolved with chitosan is mixed with hyaluronic acid solution.
Alternative scheme is: can hyaluronic acid and/or collagen be dissolved in the chitosan solution in the step 1).
Alternative scheme is: step 2) also can adopt high temperature drying, common drying means such as air-dry.
Alternative scheme is: step 3) can adopt common sterilization methods such as high-temperature sterilization, oxirane disinfection, ultraviolet disinfection.
Alternative scheme is: dry after obtaining the sponge of chitosan and/or collagen with taking out behind the 1-60min clock in its immersion hyaluronic acid solution, obtain hemostatic composition.
Alternative scheme is: dry after obtaining the sponge of hyaluronic acid and/or collagen with taking out behind the 1-60min clock in its immersion chitosan solution, obtain hemostatic composition.
Present technique compared with prior art has following advantage and beneficial effect:
Chitosan is the unique cationic polysaccharide that contains amino of occurring in nature, can attract electronegative platelet and erythrocyte.Because amino hydrophilic can promote the quantity that Fibrinogen adsorbs, thereby platelet increasing adheres to and thrombosis.Many hollow structures of the spongy hemostatic material that obtains after the lyophilization can be induced infiltration and the propagation of repair cell in dressing, cover but the long period is used for wound surface, and have the effect of tangible promotion wound healing.Chitosan is the de-acetyl chitin product that extensively is present in plant cell wall and Crustacean and the insecticide, and its catabolite is nontoxic, and can be absorbed fully by organism.
Collagen protein is a kind of important extracellular matrix protein, is the key component of vertebrates and invertebrates supporting structure.In human body, it is a topmost protein in skin, skeleton, cartilage and the connective tissue.It keeps aspects such as biological and structural intergrity to have important effect at tissue and organ (as: bone, skin, tendon, blood vessel and cartilage etc.).
Hyaluronic acid is the main component that constitutes connective tissues such as matter, vitreum, knuckle synovia between human body cell, brings into play water conservation in vivo, keeps extracellular space, regulates osmotic pressure, lubricated, the important physiological function that promotes cytothesis.Contain a large amount of carboxyls and hydroxyl in the hyaluronan molecule.Hyaluronic acid is used for prevention of postoperative adhesion and the healing that promotes skin wound.Biocompatibility is excellent, and its catabolite is nontoxic, and can be absorbed fully by organism.
Because chitosan has good biocompatibility and biodegradable performance; Be the chitinous product that takes off acetyl; Deacetylation is big more, and its surperficial amino content is high more, and hydrophilic and biocompatibility are had very big influence; The present invention uses high deacetylized chitosan (up to 95%), makes the biocompatibility of whole sthptic sponge and hemostasis and pain-relieving function significantly improve.
The present invention selects for use hyaluronic acid and chitosan to be main hemostasis substrate, and preparing can the novel sthptic sponge of quick-acting haemostatic powder, and great economic and social benefit is arranged.
Description of drawings
Fig. 1 product of the present invention contrasts with similar functional product amount of bleeding;
Fig. 2 product of the present invention compares with similar functional product bleeding stopping period effect;
Can find out that from table 1 our product can effectively stop blooding, performance is superior to like product.
Can find out that from table 2 product of the present invention has the effect of quick-acting haemostatic powder than similar functional product, haemostatic effect is superior to like product.
The specific embodiment
Below in conjunction with embodiment the present invention is done further detailed description.
Embodiment 1
With 1 gram deacetylation is that 40% chitosan (molecular weight is between 20,000-300,000) and/or 0.1 gram collagen are dissolved in 100ml 0.2% (v/v) acetum; Add 0.1 gram hyaluronic acid behind the room temperature high-speed stirred 10min; Continue room temperature high-speed stirred 10min, place rectangular die, and after placing refrigerator and cooled to freeze 60min; Place the freezer dryer lyophilization, obtain required spongy hemostatic composition after adopting Co60 roentgenization sterilization then.
Embodiment 2
With 1 gram deacetylation is that 60% chitosan (molecular weight is between 100,000-500,000) and/or 0.1 gram collagen are dissolved in 100ml 1% (v/v) acetum; Add 1wt% hyaluronic acid solution 50ml; Behind the room temperature high-speed stirred 10min; Place rectangular die, place 50-200 degree centigrade of environment to obtain spongy hemostatic composition after 12 hours, spongy hemostatic composition is obtained required sthptic sponge after with disinfection by ultraviolet light.
Embodiment 3
With 1 gram deacetylation is that 80% chitosan (molecular weight is between 0.5 ten thousand-200,000) and/or 1 gram collagen are dissolved in 100ml 2% (v/v) acetum; And adding 2wt% sodium hyaluronate solution 100ml continuation room temperature high-speed stirred 20min is placed in the square mould; Place refrigerator and cooled to freeze the 120min postlyophilization compositions, obtain required sthptic sponge behind the employing oxirane disinfection.
Embodiment 4
With 5 gram deacetylations is that 92% chitosan (molecular weight is between 500,000-1,000,000) and/or 0.1 gram collagen are dissolved in 100ml 3% (v/v) acetum, and room temperature high-speed stirred 10min is placed in the rectangular die, obtains spongy chitosan after the lyophilization.With spongy chitosan as for after fully soaking into 5min in the 1wt% sodium hyaluronate solution; Obtain spongy A in 50 degrees centigrade of oven dry, again with A immerse in the 1wt% sodium hyaluronate solution fully soak into 5min after, in 50 degrees centigrade of oven dry; 2-10 time so repeatedly; Obtain spongy hemostatic composition, behind the Co60 illumination-based disinfection, obtain required hemostatic composition.
Embodiment 5
50ml5wt% decarboxylation methyl chitosan aqueous solution and/or 0.1 gram are mixed with the 50ml2wt% sodium hyaluronate solution, and high-speed stirred obtains mixed solution A under the room temperature.Mixed solution A is placed square dies, in subzero 2 degrees centigrade freezing 3 as a child, place freezer dryer lyophilization 8 as a child to take out, behind the Co60 illumination-based disinfection, obtain required hemostatic composition then.
Embodiment 6
5 gram carboxymethyl chitosans (molecular weight is between 500,000-1,000,000) and/or 0.1 gram collagen are dissolved in the 50ml distilled water, and room temperature high-speed stirred 10min is placed in the rectangular die, obtains sponge A after the lyophilization.Will
A is as for after fully soaking into 5min in the 1wt% sodium hyaluronate solution; Obtain spongy A in 50 degrees centigrade of oven dry, again with A immerse in the 1wt% sodium hyaluronate solution fully soak into 5min after, in 80 degrees centigrade of oven dry; 2-10 time so repeatedly; Obtain hemostatic composition, after the ethane via epoxyethane sterilization, obtain required hemostatic composition.
Embodiment 7
Place square dies in the solution with 50ml 5wt% hyaluronate sodium and/or 0.1 gram collagen, in 60 degrees centigrade of held 10 hours, oven dry obtained A; Again with A immerse in the 5wt% carboxymethyl chitosan sugar juice fully soak into 5min after; In 50 degrees centigrade of oven dry, 2-10 time so repeatedly, obtain compositions B; Behind the Co60 illumination-based disinfection, obtain required hemostatic composition.
Place square dies in the solution with 50ml 5wt% hyaluronate sodium and/or 0.1 gram collagen, in 60 degrees centigrade of held 10 hours, oven dry obtained A; Again with A immerse in the 5wt% carboxymethyl chitosan sugar juice fully soak into 5min after; In 50 degrees centigrade of oven dry, 2-10 time so repeatedly, obtain compositions B; Behind the Co60 illumination-based disinfection, obtain required hemostatic composition.
Hemostatic composition product of the present invention through repeatedly experiment discovery, all has excellent haemostatic effect to the effect of different parts and different wounds.The described method for preparing hemostatic material of the application of the invention, prescription is simple, and preparation technology is prone to row.
Above content is to combine concrete preferred implementation to the further explain that the present invention did, and can not assert that practical implementation of the present invention is confined to these explanations.For the those of ordinary skill of technical field under the present invention, under the prerequisite that does not break away from the present invention's design, can also make some simple deduction or replace, all should be regarded as belonging to protection scope of the present invention.
Claims (9)
1. absorbable hemostatic composition, it is characterized in that: comprise hyaluronic acid, collagen and chitosan, hyaluronic acid, collagen and chitosan three weight ratio are 0.01～100:0.01～100) 1.
2. absorbable according to claim 1 hemostatic composition; It is characterized in that: described hyaluronan molecule amount is 10,000-5,000,000; Described collagen is that the deacetylation of described chitosan is 40-95% from the humanized's of the animal derived collagen of cattle, pig, fish extraction and/or reorganization collagen and/or collagen fragment.
3. the preparation technology of an absorbable hemostatic composition is characterized in that: comprise the steps:
1): at least a being dissolved in the chitosan solution with in hyaluronic acid or the collagen obtains mixed solution A behind the room temperature high-speed stirred 1-100min
2): A is placed the hemostasis mould, form sthptic sponge B after the lyophilization
3): B obtains finished product after sterilization.
4. preparation technology like the said absorbable hemostatic composition of claim 3; It is characterized in that: chitosan and/or collagen are dissolved in the acid solution such as acetum or formic acid solution of 0.1-30% (v/v), the acid solution that is dissolved with chitosan and/or collagen is mixed with hyaluronic acid solution.
5. the preparation technology of an absorbable hemostatic composition; It is characterized in that: hyaluronic acid and collagen are dissolved in the chitosan solution; Chitosan and hyaluronic weight ratio are 0.01～100:0.01～100:1 in the solution, obtain mixed solution A behind the room temperature high-speed stirred 1-100min.
6. preparation technology like the said absorbable hemostatic composition of claim 3 is characterized in that: obtain adopting behind the finished product high temperature, air-dry drying means.
7. preparation technology like the said absorbable hemostatic composition of claim 3 is characterized in that: the sterilization of step 3 is the sterilization methods that adopt high-temperature sterilization, oxirane disinfection, ultraviolet disinfection, and said ultraviolet rays irradiation is 1-120min.
8. the preparation technology like the said absorbable hemostatic composition of claim 3 is characterized in that: after obtaining the sponge of chitosan and/or collagen, with taking out drying behind the 1-60min clock in its immersion hyaluronic acid solution, obtain hemostatic composition.
9. the preparation technology like the said absorbable hemostatic composition of claim 3 is characterized in that: after obtaining the sponge of hyaluronic acid and/or collagen, with taking out drying behind the 1-60min clock in its immersion chitosan solution, obtain hemostatic composition.
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| CN2011100215156A CN102600495A (en) | 2011-01-19 | 2011-01-19 | Absorbable hemostatic composition and preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319744A (en) * | 2013-05-08 | 2013-09-25 | 江苏德威兰医疗器械有限公司 | Hemostasis sponge and preparation method thereof |
| GB2509588A (en) * | 2012-11-07 | 2014-07-09 | Medtrade Products Ltd | A wound care device comprising an acid, and a method of treating said device with ethylene oxide |
| CN110585139A (en) * | 2019-10-12 | 2019-12-20 | 青岛世泽生物技术有限公司 | Preparation process of bacteriostatic balanced adsorption dry and comfortable velvet for women |
| CN112675353A (en) * | 2020-12-30 | 2021-04-20 | 江苏聚源医疗技术有限公司 | Recombinant collagen dressing and preparation method thereof |
| CN112957274A (en) * | 2021-02-04 | 2021-06-15 | 甘肃天际生物科技有限公司 | Recombinant collagen freeze-dried ball and preparation process thereof |
| EP3925636A1 (en) | 2020-06-17 | 2021-12-22 | Centre Of Experimental Medicine Slovak Academy Of Sciences Institute Of Experimental Pharmacology | Composite membranes containing a smart-released cytoprotectant targeting the inflamed tissue and use thereof |
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| CN1461658A (en) * | 2002-05-31 | 2003-12-17 | 暨南大学 | Biological induction type active artificial cornea, and application method therefor |
| CN1589912A (en) * | 2003-09-02 | 2005-03-09 | 王春正 | Adhere proof material capable of absorbing, disintegrating and hemostasis |
| CN1820789A (en) * | 2006-03-13 | 2006-08-23 | 西北大学 | Biological degradable hemostatic sponge material and its preparing method |
| CN101700409A (en) * | 2009-11-20 | 2010-05-05 | 佘振定 | Material prepared from purely natural material and used for wounds |
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2011
- 2011-01-19 CN CN2011100215156A patent/CN102600495A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1461658A (en) * | 2002-05-31 | 2003-12-17 | 暨南大学 | Biological induction type active artificial cornea, and application method therefor |
| CN1589912A (en) * | 2003-09-02 | 2005-03-09 | 王春正 | Adhere proof material capable of absorbing, disintegrating and hemostasis |
| CN1820789A (en) * | 2006-03-13 | 2006-08-23 | 西北大学 | Biological degradable hemostatic sponge material and its preparing method |
| CN101700409A (en) * | 2009-11-20 | 2010-05-05 | 佘振定 | Material prepared from purely natural material and used for wounds |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2509588A (en) * | 2012-11-07 | 2014-07-09 | Medtrade Products Ltd | A wound care device comprising an acid, and a method of treating said device with ethylene oxide |
| GB2509588B (en) * | 2012-11-07 | 2017-07-19 | Medtrade Products Ltd | Wound care device |
| CN103319744A (en) * | 2013-05-08 | 2013-09-25 | 江苏德威兰医疗器械有限公司 | Hemostasis sponge and preparation method thereof |
| CN103319744B (en) * | 2013-05-08 | 2016-08-10 | 江苏德威兰医疗器械有限公司 | A kind of sthptic sponge and preparation method thereof |
| CN110585139A (en) * | 2019-10-12 | 2019-12-20 | 青岛世泽生物技术有限公司 | Preparation process of bacteriostatic balanced adsorption dry and comfortable velvet for women |
| EP3925636A1 (en) | 2020-06-17 | 2021-12-22 | Centre Of Experimental Medicine Slovak Academy Of Sciences Institute Of Experimental Pharmacology | Composite membranes containing a smart-released cytoprotectant targeting the inflamed tissue and use thereof |
| CN112675353A (en) * | 2020-12-30 | 2021-04-20 | 江苏聚源医疗技术有限公司 | Recombinant collagen dressing and preparation method thereof |
| CN112957274A (en) * | 2021-02-04 | 2021-06-15 | 甘肃天际生物科技有限公司 | Recombinant collagen freeze-dried ball and preparation process thereof |
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Application publication date: 20120725 |